Carboplatin plus Paclitaxel in Combination with the Histone Deacetylate Inhibitor, Vorinostat, in Patients with Recurrent Platinum-Sensitive Ovarian Cancer
<b>Background:</b> This phase II study evaluated the efficacy and safety of the histone deacetylase (HDAC) inhibitor, vorinostat, administered in combination with paclitaxel and carboplatin in patients with platinum sensitive recurrent ovarian cancer. <b>Methods:</b> Women wi...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-02-01
|
| Series: | Journal of Clinical Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0383/13/3/897 |
| _version_ | 1797318543345188864 |
|---|---|
| author | Hanieh Meteran Anja Ør Knudsen Trine Lembrecht Jørgensen Dorte Nielsen Jørn Herrstedt |
| author_facet | Hanieh Meteran Anja Ør Knudsen Trine Lembrecht Jørgensen Dorte Nielsen Jørn Herrstedt |
| author_sort | Hanieh Meteran |
| collection | DOAJ |
| description | <b>Background:</b> This phase II study evaluated the efficacy and safety of the histone deacetylase (HDAC) inhibitor, vorinostat, administered in combination with paclitaxel and carboplatin in patients with platinum sensitive recurrent ovarian cancer. <b>Methods:</b> Women with recurrent platinum-sensitive ovarian, peritoneal, or Fallopian tube carcinoma, a performance status of 0–2, and good overall organ function were eligible. Patients received 6 courses of paclitaxel (175 mg/m<sup>2</sup>) and carboplatin area under the curve (AUC) of 5.0 mg/mL/min administered via intravenous infusion on day 1 of a 3-week schedule. In addition, patients received vorinostat 400 mg orally once daily on days −4 through 10 of Cycle 1 and days 1 through 14 of each subsequent treatment cycle. The primary endpoints were progression-free survival (PFS) and adverse events. The secondary endpoints were the objective response rate and overall survival. <b>Results:</b> Fifty-five patients were included. CR was obtained in 14 patients (26.4%) and PR in 19 patients (35.8%), resulting in an ORR of 62.2%. Twenty patients (37.7%) had SD. The median duration of response (DoR) was 12.6 (range 6–128) months. The median PFS was 11.6 months (95% CI, 10.3–18.0; <i>p</i> < 0.001). Median OS was 40.6 months (95% Cl, 25.1–56.1). The most common treatment-related adverse events (all grades) were fatigue, anemia, thrombocytopenia, neutropenia, anorexia, nausea, pain, sensory neuropathy, myalgia, stomatitis and diarrhea. <b>Conclusions:</b> Vorinostat combined with carboplatin plus paclitaxel was tolerable and generated significant responses including a long median overall survival in recurrent platinum-sensitive ovarian cancer. |
| first_indexed | 2024-03-08T03:53:57Z |
| format | Article |
| id | doaj.art-b16797c7e0f8462f9dff526026ace7c1 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-08T03:53:57Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-b16797c7e0f8462f9dff526026ace7c12024-02-09T15:16:45ZengMDPI AGJournal of Clinical Medicine2077-03832024-02-0113389710.3390/jcm13030897Carboplatin plus Paclitaxel in Combination with the Histone Deacetylate Inhibitor, Vorinostat, in Patients with Recurrent Platinum-Sensitive Ovarian CancerHanieh Meteran0Anja Ør Knudsen1Trine Lembrecht Jørgensen2Dorte Nielsen3Jørn Herrstedt4Department of Clinical Oncology and Palliative Care, Zealand University Hospital, 4000 Roskilde, DenmarkDepartment of Oncology, Odense University Hospital, 5000 Odense, DenmarkDepartment of Oncology, Odense University Hospital, 5000 Odense, DenmarkDepartment of Oncology, Copenhagen University Hospital, Herlev and Gentofte Hospital, 2730 Copenhagen, DenmarkDepartment of Clinical Oncology and Palliative Care, Zealand University Hospital, 4000 Roskilde, Denmark<b>Background:</b> This phase II study evaluated the efficacy and safety of the histone deacetylase (HDAC) inhibitor, vorinostat, administered in combination with paclitaxel and carboplatin in patients with platinum sensitive recurrent ovarian cancer. <b>Methods:</b> Women with recurrent platinum-sensitive ovarian, peritoneal, or Fallopian tube carcinoma, a performance status of 0–2, and good overall organ function were eligible. Patients received 6 courses of paclitaxel (175 mg/m<sup>2</sup>) and carboplatin area under the curve (AUC) of 5.0 mg/mL/min administered via intravenous infusion on day 1 of a 3-week schedule. In addition, patients received vorinostat 400 mg orally once daily on days −4 through 10 of Cycle 1 and days 1 through 14 of each subsequent treatment cycle. The primary endpoints were progression-free survival (PFS) and adverse events. The secondary endpoints were the objective response rate and overall survival. <b>Results:</b> Fifty-five patients were included. CR was obtained in 14 patients (26.4%) and PR in 19 patients (35.8%), resulting in an ORR of 62.2%. Twenty patients (37.7%) had SD. The median duration of response (DoR) was 12.6 (range 6–128) months. The median PFS was 11.6 months (95% CI, 10.3–18.0; <i>p</i> < 0.001). Median OS was 40.6 months (95% Cl, 25.1–56.1). The most common treatment-related adverse events (all grades) were fatigue, anemia, thrombocytopenia, neutropenia, anorexia, nausea, pain, sensory neuropathy, myalgia, stomatitis and diarrhea. <b>Conclusions:</b> Vorinostat combined with carboplatin plus paclitaxel was tolerable and generated significant responses including a long median overall survival in recurrent platinum-sensitive ovarian cancer.https://www.mdpi.com/2077-0383/13/3/897ovarian cancerplatinum-sensitive recurrencehistone deacetylase inhibitorvorinostat |
| spellingShingle | Hanieh Meteran Anja Ør Knudsen Trine Lembrecht Jørgensen Dorte Nielsen Jørn Herrstedt Carboplatin plus Paclitaxel in Combination with the Histone Deacetylate Inhibitor, Vorinostat, in Patients with Recurrent Platinum-Sensitive Ovarian Cancer Journal of Clinical Medicine ovarian cancer platinum-sensitive recurrence histone deacetylase inhibitor vorinostat |
| title | Carboplatin plus Paclitaxel in Combination with the Histone Deacetylate Inhibitor, Vorinostat, in Patients with Recurrent Platinum-Sensitive Ovarian Cancer |
| title_full | Carboplatin plus Paclitaxel in Combination with the Histone Deacetylate Inhibitor, Vorinostat, in Patients with Recurrent Platinum-Sensitive Ovarian Cancer |
| title_fullStr | Carboplatin plus Paclitaxel in Combination with the Histone Deacetylate Inhibitor, Vorinostat, in Patients with Recurrent Platinum-Sensitive Ovarian Cancer |
| title_full_unstemmed | Carboplatin plus Paclitaxel in Combination with the Histone Deacetylate Inhibitor, Vorinostat, in Patients with Recurrent Platinum-Sensitive Ovarian Cancer |
| title_short | Carboplatin plus Paclitaxel in Combination with the Histone Deacetylate Inhibitor, Vorinostat, in Patients with Recurrent Platinum-Sensitive Ovarian Cancer |
| title_sort | carboplatin plus paclitaxel in combination with the histone deacetylate inhibitor vorinostat in patients with recurrent platinum sensitive ovarian cancer |
| topic | ovarian cancer platinum-sensitive recurrence histone deacetylase inhibitor vorinostat |
| url | https://www.mdpi.com/2077-0383/13/3/897 |
| work_keys_str_mv | AT haniehmeteran carboplatinpluspaclitaxelincombinationwiththehistonedeacetylateinhibitorvorinostatinpatientswithrecurrentplatinumsensitiveovariancancer AT anjaørknudsen carboplatinpluspaclitaxelincombinationwiththehistonedeacetylateinhibitorvorinostatinpatientswithrecurrentplatinumsensitiveovariancancer AT trinelembrechtjørgensen carboplatinpluspaclitaxelincombinationwiththehistonedeacetylateinhibitorvorinostatinpatientswithrecurrentplatinumsensitiveovariancancer AT dortenielsen carboplatinpluspaclitaxelincombinationwiththehistonedeacetylateinhibitorvorinostatinpatientswithrecurrentplatinumsensitiveovariancancer AT jørnherrstedt carboplatinpluspaclitaxelincombinationwiththehistonedeacetylateinhibitorvorinostatinpatientswithrecurrentplatinumsensitiveovariancancer |